Evidence for ETB receptor mediated pressor effects mediated by alpha‐adrenergic receptors

The hypertensive response to exogenous ET‐1 is largely mediated by ET A receptors located on vascular smooth muscle. However, there is an ET B receptor contribution, but the origin of this response is not clear. We hypothesized that stimulation of ET B receptors on neuronal tissues leads to a pressor through simulation of alpha‐adrenergic receptors. To test this hypothesis, male rats that express ET B receptors only on sympathetic nerves were anesthetized and implanted with a venous catheter for infusion of the ET B agonist sarafotoxin 6c (S6c). An arterial catheter was placed in the carotid artery for mean arterial pressure (MAP) recording and all experiments were carried out in the presence of a ganglion blocker (chlorasondamine, 5 mg/kg) to inhibit central input. Bolus i.v. infusion of S6c (0.1, 0.3, and 1.0 nmol/kg) significantly increased MAP in a dose dependent manner (ΔMAP; 7±2, 15±8, and 27±11 mmHg, respectively). In the presence of the alpha‐1 adrenergic blocker, prazosin (1mg/kg), acute infusion of S6c caused a reduction in blood pressure (ΔMAP; ‐10±2, ‐19±3, and ‐15±3 mmHg, respectively). Interestingly, beta‐adrenergic blockade (propranolol, 5mg/kg) exacerbated the pressor response to S6c (ΔMAP; 52±14, 94±5, and 82±1 mmHg, respectively).These data suggest that activation of neuronal ET B receptors causes constriction primarily through the activation of alpha‐1 adrenergic receptors while beta‐adrenergic activity opposes this response to limit ET B mediated increases in blood pressure.